I.v. fentanyl decreases the clearance of midazolam

We have examined the effect of fentanyl on the pharmacokinetics ofmidazolam in patients undergoing orthopaedic surgery. Thirty patients wereallocated randomly to receive fentanyl 200 micrograms and midazolam 0.2 mgkg-1 (fentanyl group, n = 15) or placebo and midazolam 0.2 mg kg-1 (placebogroup, n = 15) in a double-blind manner for induction of anaesthesia.Anaesthesia was maintained with nitrous oxide and isoflurane. Systemicclearance of midazolam was decreased by 30% (P = 0.002) and eliminationhalf-time was prolonged by 50% (P = 0.04) in the fentanyl group comparedwith the placebo group. There were no differences in the distributionhalf-time or volume of distribution at steady state between the two groups.These findings indicate that elimination of midazolam was inhibited byfentanyl during general anaesthesia.